Disease relevance of Pnp

• We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans [1].
• Deoxyguanosine toxicity in a mouse T lymphoma: relationship to purine nucleoside phosphorylase-associated immune dysfunction [2].
• Levels of adenine phosphoribosyltransferase and purine nucleoside phosphorylase in macrophages that were elicited with sodium caseinate or activated in vivo by prior intravenous injection of Listeria monocytogenes were eight times higher than those in resident cells [3].
• Conversion of 6-thioguanine to the nucleoside level by purine nucleoside phosphorylase of sarcoma 180 and sarcoma 180/TG ascites cells [4].
• Data were obtained utilizing a recombinant inbred strain, LTXBJ, and a number of newly developed LT/SvEi congenic strains.--Centromere-gene recombination was measured at 11.3 +/- 1.2% for the centromere of chromosome 7 - Gpi-1 interval and 15.8 +/- 2.4% for the centromere of chromosome 14 - Np-1 interval using the ovarian teratoma method [5].

High impact information on Pnp

• The gene encoding the T-cell receptor alpha-chain maps close to the Np-2 locus on mouse chromosome 14 [6].
• Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes [1].
• T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro [1].
• We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria [1].
• The level of three purine nucleoside metabolizing enzymes, adenosine deaminase (EC 3.5.4.4), purine nucleoside phosphorylase (EC 2.4.2.1), and adenine phosphoribosyltransferase (EC 2.4.2.7) were measured in the sonicates of different populations of mouse peritoneal macrophages [3].

Chemical compound and disease context of Pnp

• Malathion A and B esterases of mouse liver--III: In vivo effect of parathion and related PNP-containing insecticides on esterase inhibition and potentiation of malathion toxicity [7].
• Instead, the enhanced detoxification of parathion to PNP, PNPS, and PNPG likely results in the observed antagonism of parathion's acute toxicity [8].
• Ehrlich carcinomas implanted on mice were analyzed histochemically for the following enzyme activities: lactate, succinate and glucose-6-phosphate dehydrogenases, dihydrofolate reductase, purine nucleoside phosphorylase, xanthine oxidoreductase, and acid phosphatase [9].
• The zero-trans uptake of uniformly and base-labeled inosine and uridine was measured a 25 degrees C in suspensions of Novikoff rat hepatoma cells, Chinese hamster ovary cells, mouse L cells, mouse S49 lymphoma cells and a purine-nucleoside phosphorylase-deficient subline thereof (NSU-1), and in monolayer culture of mouse 3T3 and L cells [10].

Biological context of Pnp

• Progeny of an intersubspecies backcross were used to map one of these genes, Glud, proximal to Np-1 on Chromosome 14, but no restriction fragment polymorphisms could be identified for the second locus, Glud-2 [11].
• Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse [12].
• Nucleotide sequence of murine purine nucleoside phosphorylase cDNA [13].
• An RFLP found between Mus castaneus (CAST) and Mus musculus (MEV) was used to map the soluble epoxide hydrolase gene in CAST x MEV intersubspecific testcross progeny to 14 cM from the Np-1 locus on mouse chromosome 14 [14].
• The cloned murine PNP cDNA coding sequence was inserted into a mammalian expression vector under transcriptional regulation of the Moloney murine leukemia virus long terminal repeat [15].

Anatomical context of Pnp

• An improved method for detecting four Np-1 (purine nucleoside phosphorylase) alleles in mouse erythrocytes by cellulose acetate electrophoresis is described [16].
• Here we describe genomic clones encoding the constant portion of the T-cell receptor alpha-chain and map the gene to chromosome 14 in mouse, close to the gene for purine nucleoside phosphorylase (Np-2) which, in man, has been associated with T-cell immunodeficiencies [6].
• We have used a 900-bp bovine IRBP cDNA fragment to map the corresponding gene, Rbp-3, to mouse chromosome 14 with somatic cell hybrids and have positioned the gene near Np-1 (nucleoside phosphorylase-1) by analysis of the progeny of an intersubspecific backcross [17].
• Three point mutations on the Np(b) allele of the purine nucleoside phosphorylase locus in the mouse have been recovered by male germ cell mutagenesis [12].
• Northern hybridization using the murine PNP cDNA sequence as a probe identified a message of approx. 1.6 kb in mouse NIH3T3 cells which was slightly smaller than the human message observed in HeLa cells [15].

Associations of Pnp with chemical compounds

• The Adk gene was localized to bands A2 to B, Np-1 to bands B to C1, and Es-10 to bands D2 to E2 [18].
• Localization of the gene for interphotoreceptor retinoid-binding protein to mouse chromosome 14 near Np-1 [17].
• Two independent mutations of purine nucleoside phosphorylase were identified in the first-generation progeny of male mice that had been treated with the mutagen N-ethylnitrosourea and mated to untreated females [19].
• The transport was energy-dependent, inhibited by GMP-PNP and wheat germ agglutinin, but unaffected by N-ethylmaleimide [20].
• As these mice had been previously shown to excrete PNP nucleoside substrates, we examined the metabolism of deoxyguanosine [21].

Other interactions of Pnp

• Np-2 was detected by either specific activity assay or starch gel electrophoresis and shown to be linked to Es-10, 15.9 +/- 3.1 cM, on chromosome 14 [16].
• Analysis of the congenic strain B10.D2(57N)Sn confirmed this assignment and indicated that Rib-1 is closely linked to the genes encoding the T-cell receptor alpha subunit (Tcra) and nucleoside phosphorylase-2 (Np-2) [22].
• In spleen T lymphocytes, ADA and deoxyCRK activities were lower and PNP activity was about 2.5-fold higher than in the thymocytes [23].
• SSLP markers were then used to confirm the location of soluble epoxide hydrolase at 14.0 +/- 3.7 cM distal to Np-1 and 19.2 +/- 4.3 cM proximal to D14Mit7 [14].
• To isolate murine purine nucleoside phosphorylase-encoding cDNA sequences (PNP), a murine BALB/c liver cDNA library in lambda gt10 was screened for recombinants hybridizing to a human PNP cDNA probe [15].

Analytical, diagnostic and therapeutic context of Pnp

• Sequence analysis of the largest clone revealed an 867-nucleotide open reading frame encoding 289 amino acids with 84% residue identity to that encoded by human PNP and 351 bp of 3'-untranslated region [15].
• The 5' end of the murine PNP message was specifically amplified by PCR using the RACE (rapid amplification of cDNA ends) protocol, revealing a 5'-untranslated region of 78 bp [15].
• Clonal cell lines were isolated and prepro-AVP-Np-specific transcripts were detected by Northern blot hybridization analyses [24].
• Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of the cholinesterase inhibitor paraoxon (PO), p-nitrophenol (PNP), p-nitrophenyl sulfate (PNPS), and p-nitrophenyl glucuronide (PNPG) [8].
• Purine nucleoside phosphorylase heterogeneity in the mouse as analyzed by isoelectric focusing and specific activity [25].

References